Naltrexone, an opioid antagonist, is approved by the FDA for treatment of alcohol dependence. However, variable compliance with the oral formulation has limited the clinical effectiveness of the medication. To address this problem, in the current study the safety and efficacy of a sustained-release naltrexone preparation are being evaluated. A total of 180 alcohol-dependent subjects will receive naltrexone (N = 120) or placebo (N = 60) for 10 weeks. The study will also examine the association of treatment response with polymorphisms of the m opioid receptor gene (OPRM1) in subjects receiving naltrexone. A final study aim is to examine the association of polymorphisms of the d opioid receptor gene (OPRD1) with both treatment response and the diagnosis of alcohol or drug dependence in a sample of well-characterized subjects.